Dr Dietrich on the Importance of Mutational Profiling in NSCLC Treatment

Martin F. Dietrich, MD, PhD, medical oncologist, Florida Cancer Specialists & Research Institute, discusses how mutational profiling can inform subsequent treatment selection for patients with non–small cell lung cancer (NSCLC).

Current molecular testing practices in lung cancer have been substantially influenced by the expansion of actionable targeted alterations, as well as associated treatment options.

Patient risk-factors such as advanced age or heavy smoking are not predictive of specific rare mutations, and there is currently no viable tool for predicting a patient’s mutational probability according to individual characteristics, Dietrich begins.

Therefore, the optimal strategy for identifying rare mutations in patients with NSCLC is to include them in early clinical assessments, Dietrich explains. Since there are several effective first-line therapeutics for the treatment of patients with NSCLC, many of these mutations are not identified until later in the disease course, if at all, he adds. There is a clear algorithm for the use of these first-line options for common mutations like EGFR and ALK, Dietrich continues. Although there are also agents approved for mutations like RET, ROS1, and BRAF, it is more difficult to determine their proper sequencing, Dietrich states.

In clinical practice, the selection of targeted therapies vs immunotherapies can be divided by KRAS and EGFR mutational status, Dietrich suggests. KRAS specifically may be associated with higher mutational burden and smoking, he notes. However, there is some overlap according to disease biology, and some mutations cannot be definitively clustered due to a lack of phase 3 data, Dietrich qualifies. For example, targeted therapies appear to provide more benefit for patients with NSCLC exhibiting a RET fusion based on observational studies and biological analysis, he details.

Accordingly, patients who may or may not be enriched for specific mutations should not be selected out. Instead, all patients should undergo next-generation sequencing using both DNA- and RNA-based platforms regardless of disease stage, Dietrich concludes.